Gene expression during spermatogenesis in mammals is being examined to define intrinsic and extrinsic mechanisms regulating development and function of male gametes. Genes being studied are expressed uniquely in spermatogenic cells and/or during specific stages of their development. The code for germ cell-specific isoforms of known proteins and include genes for glycolytic enzymes and proteins involved in cell-cell interaction. For example, cDNAs isolated hybridize with RNAs for glyceraldehyde 3-phosphate dehydrogenase (Gapd-s) and hexokinase expressed only in spermatogenic cells. The Gapd-s gene is expressed after meiosis in haploid spermatids, while expression of the hexokinase gene begins during meiosis in pachytene spermatocytes. Glucose is toxic to isolated spermatids but is required by spermatozoa for in vitro fertilization, indicating that unique regulatory processes occur for glycolysis in spermatogenic cells. In addition, mannose 6-phosphate (M6P) receptors have been identified on spermatogenic cells and shown to bind M6P-bearing ligands produced by Sertoli cells. Multiple transcripts for the cation- dependent M6P receptor in germ cells include 1.2 and 1.4 kb mRNAs not found in somatic cells. They probably arise from alternate polyadenylation signals, one being used in pachytene spermatocytes and the other in spermatids. Transgenic mice have been produced to examine the role of M6P receptors in targeting of acrosin, a sperm-specific serine protease, to the acrosome. Targeted mutations are also being used to knock out the acrosin gene to examine germ cell development and sperm function when there is a mutation in this gene. These studies also serve as models for the effects of gene mutations in humans caused by environmental agents that can be transmitted through the father to the next generation.